Comment The coronavirus pandemic began with separate viral spills — at least two but perhaps as many as two dozen — from live animals sold and slaughtered in late 2019 at the Huanan Seafood Market in Wuhan, China, according to two papers published Tuesday in the journal Science. The publication of the papers, which underwent five months of peer review and revisions by the authors, is unlikely to quell the vicious debate over how the pandemic began and whether the virus emerged from a Chinese lab. And the authors acknowledge that there are many unknowns that require further investigation—notably, which animals are involved. “Everything above that — which animals, where they came from, how they all connect — is completely unknown at this stage,” Christian Andersen, an immunologist at Scripps Research, said at a media briefing Tuesday. “Have we disproved the lab leak theory? No we do not have. Will we ever be able to? No. But there are “likely” scenarios and there are “reasonable” scenarios. … ‘Likely’ does not mean equally likely,” Andersen said. The natural origin of the pandemic – a “zoonosis” – has long been a favored theory among scientists for the simple reason that most pandemics, including the SARS coronavirus outbreak of 2002-2003, started that way. Andersen and his colleagues believe that several lines of evidence, including the clustering of early covid-19 cases in the market, make a market origin not only a possible scenario, but the only one that fits the data. The “lab leak” speculation was initially dismissed in most mainstream media as a conspiracy theory. There are many lab leak scenarios, and many have centered on the Wuhan Institute of Virology, a major research center that studies coronaviruses. Scientists there say they have never had the virus in their lab. But outside experts have questioned whether the lab adequately followed safety measures during virus research. Chinese authorities restricted access to the labs by outside researchers. Amateur sleuths created online communities that consistently raised suspicions about a potential lab leak. The push to investigate the case came amid the scientific community’s struggles to determine how the virus entered the human population. In May 2021, the journal Science published a letter from 18 scientists calling for an investigation into the origin of the virus, which would include exploring the lab leak theory. Soon after, President Biden asked his intelligence agencies to investigate all possible origins of the pandemic. The review concluded that the virus was not an engineered bioweapon, but otherwise failed to reach a conclusion about its origin. Among the scientists who signed the letter to Science was Michael Worobey, an evolutionary virologist at the University of Arizona, who thought the lab leak thesis deserved attention even if it wasn’t the most likely origin. But Worobey was soon convinced that the virus was off the market. Worobey is the lead author of the new paper arguing that the market was at the center of the pandemic. The researchers pored over data on the first patients, many of whom had direct ties to the market or lived nearby. The geography of the community’s early spread showed infections radiating outward from the area around the market, Worobey said: “It’s a crazy bull’s eye.” Additionally, when the market was first identified as the site of a cluster of cases, Chinese researchers took environmental samples looking for traces of the virus. A disproportionate number of positive virus traces came from the part of the market where live animals had been sold, the new study says. “The virus started to spread to people working in the market, but then it started to spread to the surrounding local community as vendors went to local shops and infected the people working in those shops,” Worobey suggested. Worobey is not new to this. Last year, he wrote a “Perspective” article in Science that said the geographic clustering of cases in and around the market could not be explained by “finding bias,” meaning the clustering was not simply the result of researchers knocking on doors. in this. area after locating the outbreak in the market. He believes any alternative scenario – such as a lab leak – is unlikely. “It brings us now to a point where we know Huanan Market was the epicenter of this pandemic. That much has now been established. If others want to argue with that, they are now essentially taking a pseudoscientific approach,” Worobey said in an interview Tuesday. “Even though you don’t have the smoking gun of, ‘Yeah, we sampled the raccoon virus in December,’ when you put it all together, it’s the only theory that actually explains all the data.” Angela Rasmussen, a virologist at the University of Saskatchewan and co-author of one of the new papers, said in an email that she agreed with Worobey: “There is no alternative explanation that fits the facts, so anyone trying to find one should be adept at willful ignorance, a logical falsifier or simply a storyteller’. The authors’ claim about the natural origin of the pandemic is not new: The same two documents in an earlier form were published online in February on a “preprint” site. But at that point, they existed in a peer-reviewed vacuum—something that might be reported in a news story, but without the stature of studies that have survived scrutiny by expert outsiders and journal editors. The second paper published Tuesday in Science says that genetic evidence and computer modeling suggest that the virus spread into the human population not just once, but on multiple occasions in late 2019. Genomic analysis of early cases shows two distinct lineages generations, called A and B, which were supposed to come from separate leaks. Both lineages were found in environmental samples taken at the market, according to a preprinted paper by Chinese researchers in February. Proponents of the lab leak theory counter that the market was more likely an overdistribution site. The virus could have been carried there by someone infected in a lab or someone exposed to an infected lab worker, for example. The market origin argument also rests on Chinese data that may be unreliable, Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Institute, said in an interview earlier this year. He said he thought the data was “fuzzy”. “I feel that the evidence released by the Chinese government should be taken with a healthy grain of salt,” Bloom said. There is no evidence that the virus or its immediate ancestor was in any laboratory before the outbreak in Wuhan. But the ongoing mystery of the pandemic’s origins has drawn attention to the kind of virus research — including “gain-of-function” experiments — that some critics say is too dangerous. The US National Institutes of Health, mired in controversy for helping to fund some research at the Wuhan Institute of Virology, said this year it was reviewing its policies to ensure the lab’s safety and security. Sen. Rand Paul (R-Ky.), who supports a laboratory-origin explanation, told an April 30 rally in Kentucky that if Republicans take control of the Senate after the midterm elections, he will use the subpoena power to “ get to the bottom of where this virus came from.” Chinese scientists denied that the virus was present in their laboratory. The virus, according to Andersen and other virologists who have studied it, does not appear to have been manipulated or engineered, and its genetic characteristics could have been produced through evolution. However, the controversy surrounding coronavirus research is unlikely to subside. Jeffrey Sachs, an economist at Columbia University, is leading a commission funded by the Lancet journal that is expected to produce a report this fall on the pandemic, including the origins of the virus. He recently authored an article in the Proceedings of the National Academy of Sciences calling for an investigation into the origins of the pandemic through a “bipartisan congressional inquiry with full investigative powers.” On Tuesday, after Science published the two papers, Sachs said in an email that he still supports the lab spillover theory: “The two competing hypotheses, natural diffusion and lab creation, are both viable. They should be directly compared to each other. In my opinion, the case of creating a laboratory is the simplest and most reliable.” The new documents don’t say “case closed,” but they are helpful, noted David Relman, a professor of medicine and microbiology at Stanford University who was among the signatories of the 2021 letter to Science calling for an investigation into every possible pandemic origin. He said he would like to see a similarly thorough forensic study of the lab spill case. “I don’t think we can say that we now know it started here. I think we can say that something interesting happened in that part of town,” Relman said. “We don’t have any [coronavirus] positive animals in the market”. Andersen, the Scripps Research scientist, has been embroiled in the controversy over the origin of the virus for more than two years. He was the lead author of an early paper, published in Nature Medicine, saying the virus was clearly not engineered. But his first impression of the virus was that it looked unnatural, and only after doing more research did he conclude that its features could have been produced through evolution. On Tuesday, Andersen reiterated that he initially believed the new coronavirus likely originated in a lab. But all signs now point to the market, he said. “It’s not a formal proof, again, but it’s so strong in my opinion that any other version, for example a lab leak, should be able to explain all this evidence,” he said. “It’s just not possible.”
